Neuromuscular Immunopathology Research Laboratory, Division of Neuromuscular Disease, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35294-0017, United States of America.
Heflin Center for Genomic Science, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294-0024, United States of America.
Sci Rep. 2017 Dec 12;7(1):17477. doi: 10.1038/s41598-017-17475-y.
The blood-nerve barrier (BNB), formed by tight junction-forming microvessels within peripheral nerve endoneurium, exists to regulate its internal microenvironment essential for effective axonal signal transduction. Relatively little is known about the unique human BNB molecular composition. Such knowledge is crucial to comprehend the relationships between the systemic circulation and peripheral nerves in health, adaptations to intrinsic or extrinsic perturbations and alterations that may result in disease. We performed RNA-sequencing on cultured early- and late-passage adult primary human endoneurial endothelial cells and laser-capture microdissected endoneurial microvessels from four cryopreserved normal adult human sural nerves referenced to the Genome Reference Consortium Human Reference 37 genome browser, using predefined criteria guided by known transcript or protein expression in vitro and in situ. We identified 12881 common transcripts associated by 125 independent biological networks, defined as the normal adult BNB transcriptome, including a comprehensive array of transporters and specialized intercellular junctional complex components. These identified transcripts and their interacting networks provide insights into peripheral nerve microvascular morphogenesis, restrictive barrier formation, influx and efflux transporters with relevance to understanding peripheral nerve homeostasis and pharmacology, including targeted drug delivery and the mediators of leukocyte trafficking in peripheral nerves during normal immunosurveillance.
血-神经屏障 (BNB),由周围神经内膜中的紧密连接形成的微血管形成,存在于调节其内部微环境,这对于有效的轴突信号转导至关重要。关于独特的人类 BNB 分子组成,人们知之甚少。这种知识对于理解健康状态下全身循环与周围神经之间的关系、内在或外在干扰的适应以及可能导致疾病的改变至关重要。我们对培养的早期和晚期传代成人原代人神经内膜内皮细胞进行了 RNA 测序,并对来自四个冷冻保存的正常成人腓肠神经的激光捕获微解剖神经内膜微血管进行了测序,参考基因组参考联盟人类参考 37 基因组浏览器,使用体外和原位已知转录物或蛋白质表达指导的预定义标准。我们确定了 12881 个与 125 个独立生物学网络相关的常见转录本,定义为正常成人 BNB 转录组,包括一系列全面的转运体和专门的细胞间连接复合体成分。这些鉴定的转录本及其相互作用的网络为周围神经微血管形态发生、限制屏障形成、流入和流出转运体提供了深入了解,这对于理解周围神经内稳态和药理学具有重要意义,包括靶向药物输送和白细胞在正常免疫监视期间在周围神经中的迁移介质。